title: Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.
abstract: BACKGROUND
  A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States.
  
  
  METHODS
  At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24.
  
  
  RESULTS
  In April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, -25.0%; 95% confidence interval, -121.2 to 29.3; P=0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P=0.28). The vaccine regimen had an acceptable side-effect profile.
  
  
  CONCLUSIONS
  The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer
authors.forename: Magdalena E
authors.initials: ME
authors.lastname: Sobieszczyk
authors.forename: Holly
authors.initials: H
authors.lastname: Janes
authors.forename: Shelly T
authors.initials: ST
authors.lastname: Karuna
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.forename: Doug
authors.initials: D
authors.lastname: Grove
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.forename: Chuka
authors.initials: C
authors.lastname: Anude
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Richard M
authors.initials: RM
authors.lastname: Novak
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Carter
authors.initials: C
authors.lastname: Bentley
authors.forename: Shelly
authors.initials: S
authors.lastname: Ramirez
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D055261:Immunogenetic Phenomena; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D063106:Transgender Persons; D017211:Treatment Failure; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; C584967:DNA-rAd5 vaccine; D012367:RNA, Viral; D019444:Vaccines, DNA